Mycosis fungoides (MF) is a type of primary cutaneous T-cell lymphoma [1, 2]. The anti-cluster of differentiation (CD) 30 antibody agent, brentuximab vedotin (BV), has recently been developed for specific targets against CD30-expressed tumor cells with high efficacy against various lymphomas [3–7]. Herein, we present a case of marginally CD30-expressed MF successfully treated with BV rechallenge.

A 70-year-old man with previously identified early-stage MF was treated for 2 years at another institution with skin-targeted therapies such as narrowband ultraviolet B phototherapy and etretinate or interferon-gamma. Physical examination revealed multiple dark red papules and plaques throughout the entire body (Figure 1A). F-18 fluorodeoxyglucose positron emission tomography/computed tomography revealed accumulated lesions in the cervical, parotid, and axillary lymph nodes.

A skin biopsy revealed infiltration of small to medium-sized atypical lymphoid cells occasionally admixed with larger cells in the upper dermis and often infiltrating into the epidermis (Figure 1B). Atypical lymphoid cells were positive for CD3 and CD4, and some of them (18.2%) were also positive for CD30 (Figures 1C–H). In addition to plaques more than 10% of the body surface area of the skin, numerous atypical lymphocytes or small clusters of three to six cells were observed on lymph node biopsy indicating National Cancer Institute-Lymph Nodes (NCI-LN) 2 with negative clones. Although blood involvement quantification was not possible according to the guidelines, the presence of atypical lymphocytes in the peripheral blood exceeded 5%. Furthermore, no visceral involvement was found, leading to the diagnosis of mycosis fungoides T_2BN_1AM₀B_XA, Stage ⅡB based on the recently updated classification [2, 8].

In addition to CD30-positive cells, poor prognostic factors include advanced age at onset and male sex, indicating unfavorable clinical progress. Furthermore, because oral etanercept, bexarotene, and IFN were ineffective, BV was administered by physicians in the hematology department. Eight months after BV administration, skin eruptions improved without adverse reactions.

Mycosis fungoides was maintained with a complete response to skin-targeted treatment alone for 7 months. However, skin eruption flared up and the patient was started on bexarotene treatment, which was ineffective for skin eruption and peripheral lymphoid cells (2%) and swollen lymph nodes were observed when the disease advanced into T_2AN_2AM₀B_xA, Stage IIB, according to the recently updated classification [2, 8]. BV was rechallenged for mycosis fungoides, which achieved a complete response and is still ongoing for skin eruptions.

BV is effective in patients with CD30-positive MF and primary cutaneous anaplastic large cell lymphoma. Some studies indicated that BV treatment had better response rates and progression-free survival than other treatments in patients with CD30-positive MF, and these cases were independent of the degree of CD30 expression [9].

A previous study reported the importance of rechallenge treatment with BV in Hodgkin’s lymphoma, and a reduction in the measurable tumor volume [10] was exhibited. Therefore, BV may be a candidate therapeutic option independent of CD30 expression in MF. However, further investigations are necessary to clarify the actual effects of BV treatment in these cases.